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| Mutations in PIP5K3 Are Associated with Franc¸ois-Neetens Mouchete´e Fleck Corneal Dystrophy |
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| 作者：李寿玲, … 文章来源：National Eye Institute/NIH/USA, 安徽医科大学附院眼科 230022 点击数1103 更新时间：2006/6/4 6:32:35 文章录入：window 责任编辑：毛进 |
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| Franc¸ois-Neetens fleck corneal dystrophy (CFD) is a rare, autosomal dominant corneal dystrophy characterized by numerous small white flecks scattered in all layers of the stroma. On histological examination, the corneal flecks appear to correspond to abnormal keratocytes swollen with membrane-limited intracytoplasmic vesicles containing complex lipids and acid mucopolysaccharides. Linkage analysis localized CFD to a 24-cM (18-Mb) interval of chromosome 2q35 flanked by D2S2289 and D2S126. Sequencing of numerous candidate genes in this region in affected members from 8 of 10 families showed mutations in PIP5K3, which is a large gene comprising 41 exons that span 189 kb, encodes a widely expressed 2,089-aa phosphoinositide 3-kinase family member active in post-Golgi vesicular sorting. Sequencing analysis disclosed missense, frameshift, and/or protein-truncating mutations in 8 of 10 families with CFD that were studied, including 2256delA, 2274delCT, 2709CrT (R851X), 3120CrT (Q988X), IVS19-1GrC, 3246GrT (E1030X), 3270CrT (R1038X), and 3466ArG (K1103R). The histological and clinical characteristics of patients with CFD are consistent with biochemical studies of PIP5K3 that indicate a role in endosomal sorting. |
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